In article <3433c4df.2914806 at news.mindspring.com> drew martin,
dmartin at mindspring.com writes:
>Can anyone help me understand the relationship between increased
>plasma concentrations of glutamic acid and NMDA. Is it dangerous to
>increase glutamic acid if there is an excess of NMDA?
Drew,
Glutamate is an endogenously occurring amino acid that is part of most of
the proteins made in the body. It also is secreted from nerve terminals
at synapses, where it activates glutamate receptors, usually to produce a
depolarization of the postsynaptic cell.
NMDA is *not* an endogenous substance. It is made by chemists at drug
companies. However, it can also be used to activate at least one kind of
glutamate receptor with high specificity. Therefore people usually call
this receptor the "NMDA receptor", but that shouldn't be confused with
the idea that it is really a receptor for NMDA. It's not, it's a receptor
for glutamate.
NMDA receptors depolarize the cell and also let in calcium, which can
cause all sorts of problems and can eventually lead to cell death
(excitotoxicity). Therefore, it's *possible* that increased plasma
glutamate levels might be a marker for increased glutamate at the synapse
and increased excitotoxicity. BUT, it doesn't have to mean that, and in
fact it probably doesn't. The plasma glutamate is more likely to come
from peripheral sources than central neurons, because glutamate doesn't
cross the blood brain barrier very easily. Even increased cerebrospinal
glutamate levels don't necessarily mean that there's excess glutamate at
the synapses, because there are a zillion glutamate transporter molecules
in the membranes surrounding the synapses, whose job it is to make sure
that synaptic glutamate levels stay low. In fact, if you pour a glutamate
solution into a brain or onto a slice of brain tissue, often nothing bad
at all happens to most of the neurons because these transporters are so
good at sopping it up.
Nonetheless, glutamate is bad for you and should always be avoided (that
was just a little joke - I study GABA receptors, which are infinitely
more interesting and important).
Cheers,
Matt